DESCRIPTION: The long-term objective of the research is to discover novel, biologically active and clinically useful compounds from neotropical higher plants before those sources are lost through deforestation and other habitat destruction. In this project it is proposed to identify cytotoxic and potentially chemotherapeutic compounds from plants of the Euphorbiaceae family found in the montane cloud forest at Monteverde, Costa Rica, in order to enhance the anticancer pharmacopoeia. Four seco-A triterpenoids have already been isolated from Alchornea latifolia which are cytotoxic to human liver tumors in cell culture and which are inhibitors of topomerase II, an enzyme crucial to DNA replication and cell division. Additionally crude extracts from Croton monteverdensis and Tetrorchidium costaricense were also toxic to the tumor cells. Based on these results it is hypothesized that other members of this plant family also contain cytotoxis compounds with potential for use in cancer chemotherapy. It is proposed to collect and extract leaves, bark and roots from previously unstudied Euphorbiaceae at Monteverde, Costa Rica, and to screen these extracts for the ability to kill several different tumor cell lines in culture, including hepatoma, melanoma and epidemoid carcinoma cells. Active compounds from the crude extracts will be isolated, identified and tested for activity on a number of additional tumor cell lines to prioritize them for further study. Compounds receiving high priority, i.e. those that are toxic to tumor but not to normal cells, will be submitted to the NSC tumor cell panel. Additionally mechanism based assays will be performed to determine whether the cytotoxic compounds may act by inhibiting topomerase, by affective ligand-induced typosine phosphorylation of growth factor receptor or by disruption of cellular microtubule function. These studies, it is claimed, will not only potentially identify new pharmacologic anticancer agents, but will also provide additional incentive for tropical forest preservation.